Integrated Mineral Metabolism Treatment Strategies in Patients on Dialysis

项目摘要 接受透析的终末期肾病患者矿物质代谢紊乱， 钙、磷、甲状旁腺激素和磷调节激素成纤维细胞的变化 生长因子23.临床前研究强烈表明，这些矿物质代谢异常可能 直接增加该组常见疾病的风险，包括心血管和骨骼疾病。这些 临床前研究中的潜在影响得到了患者观察性研究的支持， 代谢异常与发病率和死亡率。虽然治疗矿物质代谢 在实践中，紊乱是普遍存在的，没有明确的试验证明最好的方法， 预防透析患者的常见不良结局，如加速死亡率、心血管 疾病和频繁入院。该应用程序将利用临床实践数据以及患者 和提供者参与设计所需的试验，并克服试验成功的先前障碍，例如高风险， 矿物质代谢治疗中止率和变化率。因为（1）多个类的 药物可用于治疗矿物质代谢异常;（2）指南提倡 广泛的生化参数，如磷和甲状旁腺激素，供应商有许多 选择他们的整体方法，以矿物质代谢治疗，并证明了实质性的变化， 接近。该提案将利用来自详细医疗记录的真实实践数据， 在接受中心血液透析治疗的大量患者中， 替代治疗策略，并比较其结果。目标1将定义常见的治疗策略 其包含不同的药理学试剂组合、剂量和矿物质代谢物目标值（即， 综合策略），并使用离散选择确定该领域不同处方实践的预测因子 模型目的2将评价综合治疗策略与不良临床表现的前瞻性关联 结局，包括死亡率、心血管疾病事件、骨折、住院和健康相关 生活质量独特的数据元素，例如经常更新的药物和临床数据以及设施 聚类非常适合边际结构建模和工具变量方法，以更好地解释 潜在的混淆。在目标3中，对患者和透析护理进行焦点小组和定向访谈 供应商将被用来深入评估频繁中断和改变的根本原因， 治疗策略，困扰着以前的试验。最终，这些研究将确定替代战略， 在现实环境中实用，与最佳临床结局相关，并可持续通过 优化护理提供，从而巩固在透析这一普遍方面的实践证据基础 在乎此外，结果将选择干预和比较策略，从许多可能性， 这可能是最有效的和可持续的进一步测试在确定性的试验。

PROJECT SUMMARY Patients with end stage kidney disease on dialysis have deranged mineral metabolism, including often severe changes in calcium, phosphorus, parathyroid hormone and the phosphorus-regulatory hormone fibroblast growth factor 23. Pre-clinical studies strongly suggest that these mineral metabolism abnormalities may directly increase risk of common morbidities in this group including cardiovascular and bone disease. These potential effects in pre-clinical studies are supported by observational studies in patients linking mineral metabolism abnormalities with morbidity and mortality. Although treatment of mineral metabolism derangements is widespread in practice, there are no definitive trials demonstrating the best approaches to prevent common adverse outcomes in patients on dialysis such as accelerated mortality, cardiovascular disease and frequent hospital admissions. This application will utilize clinical practice data as well as patient and provider engagement to design needed trials and overcome prior barriers to trial success such as high rates of mineral metabolism treatment discontinuation and change. Because (1) multiple classes of pharmacologic agents are available to treat mineral metabolism abnormalities; and, (2) guidelines advocate broad ranges for biochemical parameters, such as phosphorus and parathyroid hormone, providers have many choices for their overall approach to mineral metabolism treatment and demonstrate substantial variation in approaches. This proposal will leverage real-world practice data derived from detailed medical records and linked administrative claims in a large population of patients treated with in-center hemodialysis to understand alternative treatment strategies and compare their outcomes. Aim 1 will define common treatment strategies that incorporate different pharmacologic agent combinations, doses and mineral metabolite target values (i.e., integrated strategies), and identify predictors of different prescribing practices in this area using discrete choice models. Aim 2 will evaluate the prospective association of integrated treatment strategies with adverse clinical outcomes, including mortality, cardiovascular disease events, fracture, hospitalization and health-related quality of life. Unique data elements, such as frequently updated medication and clinical data and facility clustering are well-suited to marginal structural modeling and instrumental variable methods to better account for potential confounding. In Aim 3, focus groups and directed interviews with patients and dialysis care providers will be used to deeply evaluate underlying reasons for frequent discontinuation and change of the treatment strategy that plagued prior trials. Ultimately, these studies will identify alternative strategies that are practical in real-world settings, associated with the most optimal clinical outcomes and sustainable through optimized care delivery, thereby solidifying the evidence-base for practice in this pervasive aspect of dialysis care. Additionally, results will select intervention and comparator strategies, from among many possibilities, that may be most effective and sustainable for further testing in definitive trials.